The overall objective of this project is to understand the cellular and subcellular events associated wih the regulation of the immune response in normals and in patients with autoimmune disease. Our recent studies on patients with rheumatoid arthritis (RA) or with primary Sjogren's syndrome (1 SS) using monoclonal antibodies have demonstrated that the phenotype of T-cells and B-cells at the inflammatory site (synovial membrane or salivary gland, respectively) is significantly different from those in the same patient's blood. We wish to expand our previous studies to determine the functional properties of lymphocytes at the site of tissue inflammation. Based on recent studies of autoimmune disease in mice, our studies will concentrate on the production of and response to accessory signals produced by T-cells (interluekin-2 = IL2, B-cell growth factor = BCGF, and B-cell differentiation factor = BCDF) and fragments derived from the activation of complement component C3. We will compare peripheral blood and salivary gland lymphocytes from 1 SS patients to determine the ability of: a) T-cells from each of these sites to produce IL2, BCGF and BCDF; b) B-cells from each of these sites to respond to BCGF and BCDF. Since complement fragment C3a is a potent suppressor of antibody synthesis, we will investigate whether I SS lymphocytes are susceptible to this suppression. The response of lymphocytes from 1 SS patients will be compared to lymphocytes from normal volunteers and from patients with other rheumatic and neoplastic diseases. These studies will provide insight into the cellular and subcellular events leading to lymphocyte activation and autoimmune tissue destruction. Our results could lead to clinically valuable insights such as how to modulate the immune system to control autoimmune and neoplastic disease.